THE ROLE OF VOLUME DEPLETION, ANTI-DIURETIC HORMONE AND ANGIOTENSIN-II IN THE FUROSEMIDE-INDUCED DECREASE IN MESENTERIC CONDUCTANCE IN THE DOG

Abstract

Furosemide significantly reduced mesenteric blood flow and conductance as early as 10 min after administration. When fluid losses were not replaced, conductance continued to decline. In volume-repleted animals, conductance fell initially but failed to decrease further. Furosemide decreased mesenteric conductance in 2 ways: a small early decrease which was not related to volume loss and a later more marked decrease which was related to volume loss. The initial decrease in conductance seen in furosemide-treated animals appears to be mediated via the renin-angiotensin system. In volume-repleted as well as volume-depleted animals, the plasma concentrations of renin and angiotensin II, but not antidiuretic hormone, were increased 10 min after furosemide administration. Inhibitors of the renin-angiotensin system abolished the response. The later decrease in mesenteric conductance induced by furosemide was more complex. When fluid losses were not replaced, plasma levels of angiotensin II and renin, as well as antidiuretic hormone, increased 40 min after furosemide administration. Neither an infusion of Sar1-Ile8-angiotensin II nor hypophysectomy, alone, prevented the furosemide-induced decrease in conductance. The decreased conductance was reversed when Sar1-Ile8-angiotensin II was infused into hypophysectomized dogs. The later more marked decrease in conductance induced by furosemide was related to 3 factors: volume loss, plasma concentration of angiotensin II and plasma concentration of antidiuretic hormone. Mesenteric conductance was decreased by furosemide if plasma concentrations of 1 or both vasoactive factors were elevated in the presence of a decrease in extracellular volume.